Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-[kappa]B Activation

Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in...

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Published in:Mediators of inflammation 2017-01, Vol.2017
Main Authors: Endale, Mehari, Kim, Tae-Hwan, Kwak, Yi-Seong, Kim, Na-Mi, Kim, Seung-Hyung, Cho, Jae Youl, Yun, Bong-Sik, Rhee, Man-Hee
Format: Article
Language:English
Subjects:
Arthritis
Care and treatment
Cytokines
Health aspects
Inflammation
Kinases
Ligands
Natural products
Phosphorylation
Physiological aspects
Properties
Proteins
R&D
Research & development
Sesquiterpenes
Studies
T cell receptors
Transcription factors
Tumor necrosis factor-TNF
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Summary:Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS- stimulated RAW 264.7 macrophages. The involvement of NF-[kappa]B and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, [PGE.sub.2], COX-2, NF-[alpha], IL-1[beta], IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, [P38.sup.MAPK], and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF- [kappa]B and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I- [kappa]B[alpha] degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-[kappa]B and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti- inflammatory agent.
ISSN:0962-9351
1466-1861
DOI:10.1155/2017/7250968